Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

Age bias in survey sampling and implications for estimating HIV prevalence in men who have sex with men: insights from mathematical modelling.

Respondent-driven sampling (RDS) is widely used to estimate HIV prevalence in men who have sex with men (MSM). Mathematical models that are calibrated to these data may be compromised if they fail to account for selection biases in RDS surveys. To quantify the potential extent of this bias, an agent-based model of HIV in South Africa was calibrated to HIV prevalence and sexual behaviour data from South African studies of MSM, first reweighting the modelled MSM population to match the younger age profile of the RDS surveys (age-adjusted analysis) and then without reweighting (unadjusted analysis). The model estimated a median HIV prevalence in South African MSM in 2015 of 34.6% (inter-quartile range (IQR): 31.4-37.2%) in the age-adjusted analysis, compared with 26.1% (IQR: 24.1-28.4%) in the unadjusted analysis. The median lifetime risk of acquiring HIV in exclusively homosexual men was 88% (IQR: 82-92%) in the age-adjusted analysis, compared with 76% (IQR: 64-85%) in the unadjusted analysis. These results suggest that RDS studies may under-estimate the exceptionally high HIV prevalence rates in South African MSM because of over-sampling of younger MSM. Mathematical models that are calibrated to these data need to control for likely over-sampling of younger MSM.

Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity.

Leishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes ofLeishmania donovaniandLeishmania major We also report that theLeishmaniaprotease/virulence factor GP63 confers protection toLeishmaniafrom the cytolytic properties of alll-form peptides (E6, L-1018, and LL-37) but not thed-form peptide RI-1018. The results suggest that RI-1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy.

Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases.

Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA "glucocorticoid response element (GRE)". To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA "GRE". Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy.

CT-angiography for the detection of a lower gastrointestinal bleeding source.

The evaluation of lower gastrointestinal bleeding (LGIB) often involves the collaborative efforts of the gastroenterologist, radiologist, and surgeon. Efforts to localize the acute LGIB have traditionally involved colonoscopy, technetium-labeled red blood cell (RBC) scintigraphy, angiography, or a combination of these modalities. The sensitivity of each method of diagnosis is limited, with the most common cause of a negative study the spontaneous cessation of hemorrhage. Other technical factors include vasospasm, lack of adequate contrast volume or exposure time, a venous bleeding source, and a large surface bleeding area. We report the use of multidetector computed tomography (MDCT), or CT-angiography (CT-A), in the initial evaluation of LGIB, and speculate on the incorporation of this technique into a diagnostic algorithm to treat LGIB. MDCT may offer a very sensitive means to evaluate the source of acute LGIB, while avoiding some of the morbidity and intense resource use of contrast angiography, and may provide unique morphologic information regarding the type of pathology. Screening with the more rapid and available MDCT, followed by either directed therapeutic angiography or surgical management, may represent a reasonable algorithm for the early evaluation and management of acute LGIB in which an active bleeding source is strongly suspected.

Insulin restores GH responsiveness during lactation-induced negative energy balance in dairy cattle: effects on expression of IGF-I and GH receptor 1A.

Early lactation in dairy cattle is a period of severe negative energy balance (NEB) characterized by reduced blood glucose and insulin concentrations and elevated blood GH concentrations. The liver is refractory to GH during NEB and this uncoupling of the GH-IGF axis results in diminished plasma concentrations of IGF-I. Our objectives were to examine the effects of insulin administration during the immediate postpartum period on plasma IGF-I and GH concentrations and to examine the hepatic expression of total GH receptors (all GH receptor transcripts), GH receptor 1A (GHR 1A) and IGF-I. In addition, we examined adipose tissue for total GH receptor and IGF-I mRNA levels to establish the effects of chronic hyperinsulinemia on an insulin-responsive peripheral tissue. Holstein cows (n=14) were subjected to either a hyperinsulinemic-euglycemic clamp (insulin; INS) or saline infusion (control; CTL) for 96 h starting on day 10 postpartum. Insulin was infused i.v. (1 micro g/kg body weight per h), blood samples were collected hourly, and euglycemia was maintained by infusion of glucose. Insulin concentrations during the infusions were increased 8-fold in INS compared with CTL cows (2.33+/-0.14 vs 0.27+/-0.14 ng/ml (S.E.M.); P<0.001) while blood glucose concentrations were not different between treatments (45.3+/-2.2 vs 42.5+/-2.2 mg/dl; P>0.1). Plasma IGF-I increased continuously during the insulin infusion, and reached the highest concentrations at the end of the clamp, being almost 4-fold higher in INS compared with CTL cows (117+/-4 vs 30+/-4 ng/ml; P<0.001). Hepatic expression of GHR 1A and IGF-I mRNA was low in CTL cows, but was increased 3.6-fold (P<0.05) and 6.3-fold (P<0.001) respectively in INS cows. By contrast, in adipose tissue the changes in gene expression in response to insulin were reversed with decreases in both total GHR and IGF-I mRNA. The expressions of GHR 1A and IGF-I mRNA in liver tissue were correlated in INS (r=0.86; P<0.05), but not CTL cows (r=0.43; P>0.1). Insulin appears to be a key metabolic signal in coupling the GH-IGF axis, thus orchestrating a marked elevation in circulating IGF-I concentrations.

A dose-response evaluation of pipecuronium bromide in elderly patients under balanced anesthesia.

Pipecuronium bromide is a new steroidal non-depolarizing muscle relaxant currently under investigation. It is similar to pancuronium with respect to the duration of action, but lacking its cardiovascular side effects. We examined the dose-response relation of pipecuronium in 27 patients, ages 66-79 years, utilizing the incremental dose method under balanced anesthesia. The ED50, ED90 and ED95 were 22.42 (5.2) mcg/kg, 31.81 (6.9) mcg/kg and 35.12 (7.8) mcg/kg, respectively (log probit method). Our recovery data also demonstrate that residual neuromuscular blockade due to pipecuronium can easily be antagonized with neostigmine as long as spontaneous recovery of T1- at the time of reversal administration is greater than 13%. The authors conclude that under balanced anesthesia the cumulative dose-response of pipecuronium in the elderly patients is consistent with those previously described for younger population. Therefore, no dose adjustment appears necessary for the elderly. However, as with all medications, careful administration is appropriate.

Fixation of three-part proximal humeral fractures: a biomechanical evaluation.

OBJECTIVES: To examine the biomechanical stability of three constructs currently used for the management of three-part proximal humerus fractures. Tension band wires (TBW) with supplemental Enders nails, modified cloverleaf plate and screws, and intramedullary (IM) nailing with proximal and distal interlocks were tested to determine relative stability. DESIGN: A reproducible three-part fracture was made in fresh-frozen stripped proximal humeri. The fracture was stabilized using TBW/Enders nail (n = 6), plate/screws (n = 5), or IM nailing (n = 5). MAIN OUTCOME MEASUREMENTS: Mechanical testing was performed with a small preload followed by deflection of five millimeters at a rate of one millimeter per second in flexion, extension, and varus and valgus relative to the humeral shaft. A load-displacement curve was obtained. Torsional testing was performed in internal and external rotation, and torque-rotation curves were recorded. RESULTS: In cantilever bending, the plate/screws construct and the IM nail construct were superior to the TBW/Enders nail construct for all parameters except extension. There was no statistically significant difference between the IM nail and the plate/screws groups. Torsional stiffness testing revealed that the plate/screws and the IM nail were superior to the TBW/Enders nail construct. There was no statistical difference between the IM nail and the plate/screws groups. CONCLUSIONS: In a cadaveric model of three-part proximal humerus fractures stripped of soft tissue, plate/screws fixation and IM nailing provide greater torsional and bending stiffness than does fixation with TBW/Enders nail. There was no statistically significant difference in torsional or bending stiffness between IM nailing with interlocks and plate/screws fixation in this model.

Skull growth from birth to adulthood in Gilbertese on Betio.

The growth of the skull from birth till adulthood was studied among Gilbertese from Betio. With few exceptions the average head circumference was bigger in males than in females, but rarely at statistically significant levels. After the age of six months the mean head circumference of the Gilbertese fell almost invariably below the third percentile of a North American standard. The rate of growth of the skull in Gilbertese was also smaller than in North Americans, both absolutely and relative to the head circumference at birth. The possible role of early protein-energy malnutrition remained obscure.

Within herd comparison of teat dipping and dry cow therapy with only selective dry cow therapy in six herds.

A within herd comparison of teat dipping and dry cow therapy (full treatment) with only selective dry cow therapy (partial treatment) was carried out in six commercial dairy herds for a two year period. In four herds, the incidence of clinical mastitis was 2 to 12 per cent higher in the partial treatment group. In another herd, in which the pattern of clinical mastitis isolates was unusual in that minor pathogens were isolated from 30 per cent of mastitis cases, the incidence was 43 per cent higher in the partial treatment group. In the remaining herd the incidence was 10 percent higher in the full treatment group. Streptococcus uberis mastitis was more common in the partial treatment groups of five herds; coliform mastitis was more common in the full treatment groups of two herds and similar in both groups in the other herds. High rates of coliform mastitis were associated with poor herd environmental conditions but this was not true for Strep uberis mastitis. Rates of staphylococcus aureus and Strep dysgalactiae mastitis were low in all herds. The level of major pathogen infection in cows completing the trial in all herds increased in the partial treatment group from 5 per cent of quarters at the start to 12 per cent at the finish of the trial. In the full treatment group, however, there was only a small increase in this level. In contrast, levels of Corynebacterium bovis infection increased by 17 per cent in both treatment groups. Continued use of teat dipping and dry cow therapy was associated with a higher rate of coliform mastitis in two of the three herds where there were poor standards of hygiene and husbandry.

Does the use of methylmethacrylate cement in total shoulder replacement induce hemodynamic or pulmonary instability?

STUDY OBJECTIVE: To investigate whether the use of methylmethacrylate cement causes hemodynamic or pulmonary instability during total shoulder replacement surgery. DESIGN: Prospective, nonrandomized study. SETTING: Operating room. PATIENTS: 9 ASA physical status I and II patients. INTERVENTIONS: A 20-gauge radial artery catheter was placed in the wrist opposite the surgical site. Sedation with midazolam was provided, and a pulmonary artery catheter was placed through an 8.5-Fr introducer into the patient's right internal jugular vein. MEASUREMENTS AND MAIN RESULTS: Before induction of anesthesia, systolic, diastolic, and mean arterial blood pressures; heart rate; central venous pressure; systolic, diastolic, and mean pulmonary artery pressures; pulmonary capillary wedge pressure; and thermodilution cardiac output measurements were obtained. Arterial and mixed venous blood gas samples also were collected and analyzed for calculation of Qs/Qt. These hemodynamic and pulmonary parameters were measured again just before cementing of each prosthesis with methylmethacrylate cement and at 1, 5, 10, and 20 minutes after cementing. There were no statistically significant changes in any of the measured hemodynamic parameters at any time. There was no statistically significant difference in the calculated intrapulmonary shunt fraction. CONCLUSION: In this study population, the use of methylmethacrylate for total shoulder replacement was not associated with adverse hemodynamic events or increased intrapulmonary shunting.

High concentration versus incremental induction of anesthesia with sevoflurane in children: a comparison of induction times, vital signs, and complications.

STUDY OBJECTIVE: To compare sevoflurane induction times and complications in children during a high concentration, primed-circuit method and an incremental induction technique. DESIGN: Randomized, prospective open-label study. SETTING: Academic university hospital. PATIENTS: 40 unpremedicated ASA physical status I and II children age 4 months to 15 years undergoing elective surgical procedures with general anesthesia. INTERVENTIONS: Patients were randomized to one of two study groups. In the high concentration group, the anesthesia circuit was primed with 8% sevoflurane in a 2:1 nitrous oxide:oxygen (N2O:O2) mixture. Patients breathed this gas mixture spontaneously until loss of the eyelash reflex. In the incremental group, the face mask was applied and 1% sevoflurane in a 2:1 N2O:O2 mixture was administered. In this group, the sevoflurane concentration was increased by 1% every 2 to 3 breaths. Gas flows of 6 L/min were administered to both groups during the study period. Following loss of the eyelash reflex, the sevoflurane concentration was decreased to 5% until a depth of anesthesia sufficient to start an intravenous catheter was achieved. MEASUREMENTS AND MAIN RESULTS: Induction cooperation, induction time (face mask application to loss of the eyelash reflex), one-minute vital signs [blood pressure, heart rate, oxygen saturation via pulse oximetry (SpO2)], induction complications. Induction of anesthesia was faster in the high concentration group than in the incremental group (mean (SD) 42 (9) sec vs. 66 (12) sec, respectively; p < 0.001). Induction complications were minor and occurred with similar frequencies (4/20 patients vs. 3/20 patients). There were no significant intergroup heart rate, blood pressure, or SpO2 differences during induction. No patients required treatment for hypotension or bradycardia. CONCLUSIONS: In healthy pediatric patients undergoing mask induction of general anesthesia with sevoflurane, the induction time can be significantly shortened without an increase in the frequency of airway or vital sign complications using a high concentration, primed circuit technique compared with a conventional, incremental induction method.

Do heated humidifiers and heat and moisture exchangers prevent temperature drop during lower abdominal surgery?

STUDY OBJECTIVE: To compare the effects of using a heated humidifier (HH), a heat and moisture exchanger (HME), or no warming device in maintaining body temperature during surgical procedures of 1 to 4 hours' duration. DESIGN: A randomized, controlled study. SETTING: Operating room, Thomas Jefferson University Hospital, Philadelphia, PA. PATIENTS: 51 ASA physical status I, II, and III patients, age 16 to 69 years, scheduled for a variety of lower abdominal procedures under general endotracheal anesthesia anticipated to last 1 to 4 hours. INTERVENTIONS: We randomly assigned patients to receiving an HH, an HME, or no warming device during the procedure. We then measured the patient's sublingual temperature every 5 minutes prior to induction, every 15 minutes intraoperatively, and every 15 minutes postoperatively until he or she was discharged from the postanesthesia care unit, (PACU). We also measured the esophageal temperature every 15 minutes intraoperatively. MEASUREMENTS AND MAIN RESULTS: Sublingual temperature or esophageal temperature probes placed at the site of maximal heart tones indicated that the patients' temperatures dropped significantly from baseline values in all three groups during the first 60 minutes of surgery, then remained constant during the next 120 minutes of surgery. Patients who had no warming device shivered and felt cold significantly more often than patients in the HH group but not more often than patients in the HME group. There was no difference in shivering between the HH and HME groups. The patients who received an HH tended to have a higher temperature (a mean of 0.5 degrees C) throughout the study, but this did not reach statistical significance. CONCLUSIONS: Results indicate that these warming devices provide little benefit in preventing a temperature drop during procedures of 1 to 4 hours' duration, although patients with an HH tended to have a higher temperature than those with an HME or no device.

Intubating conditions after pipecuronium bromide: the influence of dose and time.

STUDY OBJECTIVE: To determine the intubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED95 (average dose that gives 95% block of the first twitch). DESIGN: To compare intubating conditions at 11/2 and 21/2 minutes in 41 patients receiving balanced anesthesia. SETTING: Surgical patients at Thomas Jefferson University Hospital. PATIENTS: Forty-one patients undergoing surgical procedure who received general anesthesia. INTERVENTIONS: After obtaining a stable baseline of train-of-four (TOF), 41 patients randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 11/2 or 21/2 minutes. MEASUREMENTS AND MAIN RESULTS: Intubating conditions at 21/2 minutes appeared significantly better than those at 11/2 minutes, regardless of the pipecuronium dose. The mean time for T1 (first twitch of TOF) to reach 50% and 90% suppression was 1.36 +/- 0.51 minutes and 2.29 +/- 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 +/- 0.27 minutes and 1.72 +/- 0.45 minutes, respectively, for the 0.1 mg/kg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of T1 was 68.2 +/- 22 minutes for the 0.07 mg/kg dose and 121.5 +/- 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. CONCLUSION: Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 11/2 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 21/2 minutes.

Sevoflurane versus halothane for general anesthesia in pediatric patients: a comparative study of vital signs, induction, and emergence.

STUDY OBJECTIVE: To compare vital signs and the speed of induction and emergence with sevoflurane versus halothane in pediatric patients. DESIGN: Prospective, randomized, open study. SETTING: Thomas Jefferson University Hospital. PATIENTS: 40 unpremedicated ASA Physical Status I and II children age 9 months to 16 years undergoing elective inpatient otorhinolaryngologic or orthopedic surgery. INTERVENTIONS: Standardized induction of anesthesia with sevoflurane (start: 1%, maximum: 7%) or halothane (start: 0.5%, maximum: 5%) in nitrous oxide/oxygen (N2O/O2). Intubation following vecuronium and 4 minutes of controlled ventilation with 2 minimum alveolar concentration (MAC) drug in O2; 1.5 MAC drug in N2O/O2 delivered for 20 minutes; then 0.75 MAC until the end of surgery. Fentanyl 1 mcg/kg was administered 15 minutes before the anticipated end of surgery, at which time anesthetics were stopped and mechanical ventilation continued until eye opening (emergence). MEASUREMENTS AND MAIN RESULTS: Blood pressure, heart rate (HR), oxygen saturation, end-tidal gas concentrations, and temperature were recorded. Induction and emergence times were measured to the nearest second. Induction (loss of eyelash reflex) was faster with sevoflurane (97 +/- 31 sec) than halothane (120 +/- 36 sec; p < 0.05), despite a lower inspired sevoflurane MAC. Emergence was faster with sevoflurane (9.9 +/- 2.9 min vs. 12.5 +/- 4.7 min; p < 0.05), despite a higher MAC multiple of end-tidal sevoflurane concentration at the end of surgery. Following intubation, HR (compared with the preinduction value in the operating room) was significantly higher in the halothane group (136.8% +/- 16.3% vs. 115.0% +/- 25.6%), as was mean arterial pressure (113.2% +/- 25.5% vs. 87.8% +/- 22.6%). This finding corresponded with a higher MAC multiple of end-tidal concentration in the sevoflurane group than in the halothane group. CONCLUSIONS: Induction of and emergence from anesthesia was faster with sevoflurane than halothane. Airway complications were low in both groups. Vital signs were more stable with sevoflurane during induction through intubation, and were comparable during maintenance. Sevoflurane is an excellent drug for inhalational induction in pediatric patients.

A comparison of desflurane and isoflurane in prolonged surgery.

STUDY OBJECTIVE: To compare desflurane with isoflurane in several anesthetic situations. DESIGN: Intubating conditions, hemodynamic response to intubation, maintenance hemodynamics, and speed of recovery from desflurane and isoflurane anesthesia were evaluated. In addition, interaction with a muscle relaxant at low and high concentrations of the anesthetics were compared. SETTING: Thomas Jefferson University Hospital. PATIENTS: Thirty-two patients who received general anesthesia for lengthy, mostly orthopedic procedures. INTERVENTIONS: Immediately after induction with thiopental sodium, desflurane or isoflurane in nitrous oxide-oxygen was administered via face mask. Anesthesia was deepened until end-tidal concentration reached 1.7 minimum alveolar concentration (MAC). The trachea was intubated without the aid of a muscle relaxant. Heart rate (HR) and blood pressure (BP) were recorded before and at 1, 2, 4, 5, and 10 minutes after intubation. Noninvasive cardiac output (CO) and systemic vascular resistance (SVR) were determined while the patient was awake, immediately before intubation, and at 5 and 10 minutes after intubation. Following intubation, the concentration of desflurane or isoflurane was lowered until the end-tidal concentration reached 0.65 MAC (low-MAC group), 1.25 MAC (high-MAC group), or 0 MAC (control group). Pancuronium bromide in 0.005 mg/kg doses was administered incrementally until T1 (first twitch of train-of-four) was depressed more than 90%. ED50 and ED95 for pancuronium with balanced anesthesia and for desflurane or isoflurane in low and high MACs, as well as speed of recovery, were determined. The time to responsiveness and awakening also was determined. MEASUREMENTS AND MAIN RESULTS: There was no significant difference between desflurane and isoflurane in intubating conditions or in BP or HR response to tracheal intubation. Both anesthetics increased HR significantly during induction. BP rose with desflurane at the preintubation point; other points showed no difference. A hyperdynamic response of increased HR and BP above 20% of baseline values was seen more frequently with desflurane (n = 7) than with isoflurane (n = 1). CO was elevated at all times after induction for low and high concentrations of both drugs, while SVR decreased over the same time with no significant difference between drugs. ED50 and ED95 for pancuronium were similar under desflurane and isoflurane at both low and high MAC, but they were significantly lower than under balanced anesthesia. Awakening times were similar for desflurane and isoflurane. CONCLUSIONS: Desflurane is similar to isoflurane in providing anesthesia for intubation and maintenance. Desflurane tends to increase HR and occasionally causes a hyperdynamic response during rapid deepening of anesthesia. It is very similar to isoflurane in its interaction with pancuronium.

The effect of contusion and cryotherapy on skeletal muscle microcirculation.

OBJECTIVE: The most common treatment of soft tissue contusions is ice application (cryotherapy). The physiological basis for this therapy is assumed to be cold-mediated vasoconstriction resulting in decreased edema formation and a reduction in overall morbidity. This proposed mechanism has not been tested. The present research examined the hypothesis that cryotherapy following contusion is effective because it reduces microvascular perfusion and subsequent edema formation. EXPERIMENTAL DESIGN: The microcirculatory responses to contusion were studied with and without cryotherapy in a chronically instrumented rat model. Initial studies evaluated the immediate effects of cryotherapy on arteriolar and venular diameters and microvascular perfusion (using laser Doppler floxmetry). Variables were measured before and immediately after 20 minutes of cryotherapy. Two additional studies monitored the same microvascular parameters longitudinally in four sets of chronically instrumented animals. Groups of rats studied had contusion or sham contusion with ice treatment or no ice treatment. Measurements were performed repeatedly before and after treatment for 24 hours or 96 hours after contusion/sham contusion. RESULTS: The acute microvascular effects of cryotherapy were vasoconstriction and decreased perfusion. However, when cryotherapy was used as a treatment following contusion/sham contusion, there were no long-lasting microvascular effects of cryotherapy either in the presence or absence of contusion. CONCLUSIONS: These results indicate that cryotherapy of striated muscle following contusion does not reduce microvascular diameters or decrease microvascular perfusion. Alternate mechanisms of action for cryotherapy treatment need to be investigated.

Run an emergency helpline.

Telephone helplines are an effective way of dealing with health related incidents in which large numbers of people need personal counselling or information for reassurance or case finding. Helplines often have to be set up at short notice, which is labour intensive and makes recruitment of appropriate staff difficult. They should ideally be part of local emergency planning resources. Doctors need to be included in the team organising the helpline to ensure that staff are properly briefed, to determine what data need to be collected, and to deal with specialised queries.

Effectiveness of atracurium in preventing succinylcholine myalgia.

A comparison was made of the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-Tubocurarine (DTC) was given prior to succinylcholine (SDC) for facilitation of tracheal intubation. The subjects were 44 ASA physical status I or II outpatient females undergoing laparoscopy. They were assigned to one of three groups: Group 1 received 0.025 mg/kg ATR; Group 2 received 0.05 mg/kg DTC, and Group 3 received saline (NS). Thiopental was administered one minute and 45 seconds after pretreatment. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. The patients were questioned one and three days postoperatively about POM and their responses recorded using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day one. The corresponding figures for DTC and NS were 59% and 43%, respectively. The difference between ATR and NS achieved statistical significance, leading to the conclusion that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. Findings suggest that ATR may be the drug of choice for the prevention of POM.